Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer
Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer
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DOI：
10.1200/jco.2006.07.0250
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发表时间：
2006-12-20
影响因子：
45.3
通讯作者：
Abdulkarim, Bassam
中科院分区：
文献类型：
--
作者：
Gabos, Zsolt;Sinha, Richie;Abdulkarim, Bassam
目的随着乳腺癌患者生存率的提高，脑转移变得越来越普遍。新诊断的人表皮生长因子受体2（HER-2）过表达乳腺癌患者脑转移的风险尚未完全确定。我们的目的是分析脑转移的风险，在新诊断的HER-2阳性乳腺癌患者与HER-2阴性patients.Patients和方法，以确定脑转移的发病率HER-2过表达的患者，我们分析了一个队列的新诊断的301 HER-2阳性和363 HER-2阴性患者之间确定1998年1月至2003年12月。采用单因素和多因素考克斯回归分析评价组织学特征与脑转移发生之间的关系。HER-2过表达乳腺癌中有9%（27例患者）发现脑转移，而HER-2阴性患者中仅为1.9%（7例患者）（风险比4.23 [1.84-9.74]，P = .0007）。HER-2过表达、肿瘤大于2 cm、至少1个阳性淋巴结和2/3级病变是脑转移的预测因素。在多因素分析中，HER-2过表达，肿瘤大小大于2 cm，和HER-2受体阴性的脑转移瘤的发展是独立的预后因素，而HER-2受体表达是protective.Conclusion我们的研究表明，新诊断的HER-2过表达乳腺癌患者脑转移的风险增加。由于大多数脑转移发生在全身性疾病发展之后，这些发现促使考虑使用能够穿过血脑屏障的HER-2抑制性小分子和/或放射学筛查以检测无症状脑转移的脑预防策略。
Purpose As survival in breast cancer patients is improving, brain metastases are becoming increasingly prevalent. The risk of brain metastases in newly diagnosed human epidermal growth factor receptor 2 (HER-2)-overexpressing breast cancer patients is not yet fully defined. We aimed to analyze the risk of brain metastasis in newly diagnosed HER-2-positive breast cancer patients in comparison with HER-2-negative patients.Patients and Methods To determine the incidence of brain metastases in HER-2-overexpressing patients, we analyzed a cohort of newly diagnosed 301 HER-2-positive and 363 HER-2-negative patients identified between January 1998 and December 2003. The association between histologic features and the occurrence of brain metastases was evaluated with univariate and multivariate Cox regression analysis.Results Median follow-up was 3.9 years. Brain metastases were identified in 9% (27 patients) with HER-2-overexpressing breast cancer compared with only 1.9% (7 patients) in the HER-2 negative patients (hazard ratio 4.23 [1.84-9.74], P = .0007). HER-2 overexpression, tumor size larger than 2 cm, at least one positive node, and grade 2/3 disease were predictors of brain metastases in univariate analysis. In multivariate analysis, HER-2 overexpression, tumor size larger than 2 cm, and hormone-receptor negativity were independent prognostic factors for the development of brain metastases, whereas hormone-receptor expression was protective.Conclusion Our study shows that newly diagnosed HER-2-overexpressing breast cancer patients are at increased risk for brain metastases. Because most brain metastases occur after the development of systemic disease, these findings prompt consideration of brain prophylaxis strategies with HER-2-inhibiting small molecules able to cross the blood-brain barrier and/or radiologic screening to detect asymptomatic brain metastases.